Cardiomyopathy is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are at risk of heart failure, arrhythmia and/or sudden cardiac death. Cardiomyopathy can often go undetected, making it especially dangerous to carriers of the disease. Cardiomyopathies can be categorized as extrinsic or intrinsic. An extrinsic cardiomyopathy is a cardiomyopathy where the primary pathology is outside the myocardium itself. Most cardiomyopathies are extrinsic, because by far the most common cause of a cardiomyopathy is ischemia. The World Health Organization calls these specific cardiomyopathies. An intrinsic cardiomyopathy is defined as weakness in the muscle of the heart that is not due to an identifiable external cause. This definition was used to categorize previously idiopathic cardiomyopathies although specific external causes have since been identified for many. The intrinsic cardiomyopathies consist of a variety of disease states, each with their own causes. Many intrinsic cardiomyopathies now have identifiable external causes including ischemia, drug and alcohol toxicity, viral infections and various genetic and idiopathic causes.
Dilated cardiomyopathy is one of the most frequent heart muscle diseases with an estimated prevalence of 1:2500. The progressive nature of this disorder is responsible for about 30-40% of all heart failure cases and is the main cause for heart transplantation in young adults. In the last decades, it was recognized that DCM has a substantial genetic contribution. It is estimated that about 30-40% of all DCM cases have a familial aggregation and until now more than 40 different genes were found to cause monogenetic DCM. However, since the course of the disease is highly variable and only a fraction of patients suffer a causal mutation, genetic modifiers are thought to play an important role (Friedrichs et al., 2009; Villard et al., 2011). Accordingly, several studies have now identified common genetic polymorphisms, which are associated with DCM or heart failure (Friedrichs et al., 2009; Villard et al., 2011). But even then, the existence of such modifiers also does not completely explain the high variability in phenotypic expression and unexplained cases of DCM.
Epigenetic mechanisms play important roles during normal development, aging and a variety of disease conditions. Numerous studies have implicated aberrant methylation in the etiology of human diseases, including cancer, MS and diabetes. Hypermethylation of CpG islands located in promoter regions of tumor suppressor genes is firmly established as the most frequent mechanism for gene activation in cancers.
Briefly, methylation of the 5′ carbon of cytosine is a form of epigenetic modification that does not affect the primary DNA sequence, but affects secondary interactions that play a critical role in the regulation of gene expression. Aberrant DNA methylation may suppress transcription and subsequently gene expression.
Disease modification through epigenetic alterations has been convincingly demonstrated for different diseases (Jones and Baylin, 2002; Feinberg and Tycko, 2004). In the cardiovascular system, histone modifications and chromatin remodelling are thought to direct adaptive as well as maladaptive molecular pathways in cardiac hypertrophy and failure (Montgomery et al., 2007) and DNA methylation was found to be responsible for the hypermutability of distinct cardiac genes (Meurs and Kuan, 2011). Furthermore, recent studies have highlighted the potential interplay between environmental factors and the disease phenotype by epigenetic mechanisms (Jirtle and Skinner, 2007; Herceg and Vaissiere, 2011). However, the knowledge about the impact of epigenetic alterations on the disease phenotype in human patients is still very limited.
Thus, epigenetic mechanisms are increasingly recognized as contributors to human disease. Surprisingly, most studies conducted so far have focused on cancer and only few have investigated the role of epigenetic mechanisms, especially DNA methylation in cardiovascular disease (Movassagh et al., 2011). However, epigenetic mechanisms are thought to control key processes such as cardiac hypertrophy, fibrosis and failure (Backs et al., 2006; Backs et al., 2008).
Furthermore, the decision to initiate or escalate therapies (drugs, devices, surgical interventions) is currently based on assumptions and supported only by few diagnostic measures (Bielecka-Dabrowa et al., 2008).
There is a need for diagnostic means and methods that not only allow the detection of a heart disease but also allow to draw conclusions about the further development of an existing heart disease or whether a heart disease will develop in a patient.